This application, submitted in response to NHLBI RFA HL-02-029, the Asthma Clinical Research Network (ACRN), proposes to use the unique combination of clinical, genomic, epidemiological, and basic scientific resources located at Wake Forest University (WFU), in the Division of Pulmonary and Critical Care Medicine, the Cloverdale Pulmonary Clinical Research Center, the Center for Human Genomics, and the Department of Public Health Sciences, in support of a Clinical Site for the Asthma Clinical Research Network. We propose two general sets of Specific Aims, the first of which describes two specific protocols for consideration by the ACRN for implementation, and the second which strives to add additional resources and value as the ACRN evolves during its second decade. Protocols: 1) The PAST Protocol (Patient-Directed versus Standard Therapy with an Inhaled Corticosteroid/Long-Acting Beta-Agonist Combination in Persistent Asthma) will test the hypothesis that patient-directed therapy using patient adjusted doses of an inhaled corticosteroid/long acting beta-agonist combination (budesonide 160 mu g/formoterol 4.5 mu g) will provide improved asthma control at less cost with increased patient satisfaction than standard, fixed-dose combination therapy (2 puffs twice a day of budesonide 160 mu g /formoterol 4.5 mu g with albuterol used as the rescue medication). 2) The SAFE Protocol (Treatment of Severe Asthma with Anti-TNF, Anti-IgE, and a Leukotriene Modifier) will test the hypothesis that treatment of patients with severe asthma, defined as those symptomatic on fluticasone 500 mu g/salmeterol 50 mu g (Advair(R) 500/50) bid, with anti-IgE (omalizumab) and/or an anti-TNF (soluble TNF receptor, etanercept) will provide better asthma control than treatment with a leukotriene receptor antagonist (LTRA, montelukast), and permit Advair(R) dose reduction to fluticasone 100 mu g/salmeterol 50 mu g in more patients in the anti-IgE and/or anti-TNF groups, than in the leuktriene receptor antagonist group. We further offer WFU resources and expertise: 1) in the Center for Human Genomics for the determination of patient genotypes and haplotypes for genetic epidemiological analysis and pharmacogenetic studies, for DNA isolation and storage, for sequencing, genotyping and haplotyping candidate genes, and determination of levels of gene expression in bronchoscopy samples; 2) identified in the Department of Public Health Sciences (PHS) to a) assist in the analysis of data collected in main ACRN protocols to answer "ancillary" questions which could be posed with the available data sets, and b) in the PHS Division of Social Science and Public Health Policy to investigate issues of health economics and patient-centered outcomes, particularly satisfaction and trust; and 3) contained within our basic science laboratories to develop and validate improved non-invasive bio-markers of airway inflammation for use in multi-center clinical trials.